We have continued our studies of the insulin-like growth factors (IGFs), their receptors and binding proteins to understand the physiological and pathological role of the IGFS. During the past year we have demonstrated that: (1) adult rat serum contains a growth hormone dependent, glycosylated IGFbinding protein (IGFBP-3), and nonglycosylated binding proteins of 30 and 24 kDa; (2) the main binding protein in fetal rat serum is IGFBP-2, which is not present in adult rat serum; (3) IGFBP-2 mRNA is expressed in all fetal rat tissues, with highest levels in liver, followed by brain and stomach. In adult rats, IGFBP-2 mRNA levels are lower in liver and other tissues, but not in brain; (4) IGFBP-L mRNA also is predominantly expressed in fetal liver, and is decreased in adult liver. Levels in fetal kidney and brain are significantly lower than IGFBP-2 mRNA; (5) IGFBP-2 mRNA is localized to the choroid plexus in adult rat brain, and IGFBP-2 is the major IGF binding protein in rat cerebrospinal fluid; (6) In the brain of midgestational rat embryos, IGFBP-2 mRNA is expressed in the choroid plexus epithelium, the progenitor of the posterior pituitary, and the floor plate. IGF-H mRNA is expressed in some adjacent cells (the choroid mesenchyme and progenitors of the anterior and intermediate lobes of the pituitary), but not in the floor plate; (7) IGFBP-2 was identified in a human rhabdomyosarcoma cell line and in human cerebrospinal fluid; (8) In adult rat liver, IGFBP-2 mRNA is increased 10-fold after hypophysectomy, fasting, or streptozotocin diabetes; IGFBP-L mRNA is not increased after hypophysectomy, is increased after prolonged fasting, and is increased 100-fold in diabetes; (9) In a rat hepatoma cell line, dexamethasone increases IGFBP- I gene transcription; (1 0) IGF-II is an autocrine growth factor for a human neuroblastoma cell line, and acts via the IGF-I receptor; (I 1) IGF-I stimulates motility of a human melanoma cell Ene via the IGF-I receptor.